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1.
Obesity and the metabolic syndrome and their associated morbidities are major public health issues, whose prevalence will continue to increase in the foreseeable future. Aberrant signaling by the receptors for leptin and insulin plays a pivotal role in development of the metabolic syndrome. More complete molecular-level understanding of how both of these key signaling pathways are regulated is essential for full characterization of obesity, the metabolic syndrome, and type lI diabetes, and for developing novel treatments for these diseases. Phosphorylation of proteins on tyrosine residues plays a key role in mediating the effects of leptin and insulin on their target cells. Here, we discuss the molecular methods by which protein tyrosine phosphatases, which are key physiological regulators of protein phosphorylation in vivo, affect signaling by the leptin and insulin receptors in their major target tissues.  相似文献   

2.
Obesity has been reported to increase postmenopausal breast cancer risk by 30% to 50%, and obese breast cancer patients have been shown to present more aggressive breast cancer pathological features As most breast cancers are sex hormone-dependent, adipocytokines derived from adipose tissue, such as leptin, may account for the positive association between obesity and breast cancer. Leptin, a 16-kDa protein product of the obese gene, was initially regarded as a neuroendocrine factor in the hypothalamus to maintain homeostasis of body weight by regulating food intake and energy expenditure.  相似文献   

3.
Lipids are important constituents of the neuronal membrane. Also, kinds of fatty acids were supplied in the diet can affect the brain growth and the onset of myelinogenesis. So, in this study, the effect of oleic acid and palmitic acid on sensorimotor coordination and cerebellum histological changes was investigated. In present study, 9 groups (10 rats in each group) of Wistar immature rats were used. One group kept as control with similar environmental conditions to other groups. Four groups of rats were fed with diet containing 10% palmitic acid for 1 to 4 weeks respectively. Four groups of rats were fed with diet containing 10% oleic acid for 1 to 4 weeks respectively. After maturation (age at 90 weeks), the rats were tested for motor activity task by using Rota rod based on standard method and then the whole cerebellum were removed and samples were fixed in bouin for routine paraffin embedding method. The results showed that sensorimotor coordination was significantly (p 〈 0.01) increased in rats fed with oleic acid for 4 weeks. The sensorimotor coordination was significantly (p 〈 0.01, p 〈 0.5) increased in groups received palmitic acid for 1 and 2 weeks. Also, diameter of cerebellum was significantly (p 〈 0.001, p 〈 0.5) changed with oleic acid for 4 weeks and palmitic acid for 2 weeks. The diameter of molecular layer of cerebellum was significantly (p 〈 0.001, p 〈 0.5) changed with oleic acid for 2 and 4 weeks. Thus, palmitic and oleic acid can improve function of tissue of cerebellum in rat.  相似文献   

4.
High blood glucose level can increase the production of free radicals and the AGEs. Flavonoids from fruits and vegetables can prevent that events because they have antioxidant and hypoglycemic effects. The aim of this study was to examine possible hypoglycemic and antioxidant effect of the ethanol extract of purple sweet potato tubers. Subject of this study were 20 male adult rats divided into 4 groups with randomized pre-test and post-test control group design. Before treatment, blood samples were collected from retro-orbital sinus of all rats for blood glucose, MDA and total antioxidant measurement as pre-test data. After pre-test, group 1 (control group) rats were given normal diet without ethanol extract of purple sweet potato tubers. Group 2, 3, and 4 rats were given normal diet and ethanol extract of purple sweet potato tubers 1 cc/day, 2 cc/day, 4 cc/day, respectively, for one week. After one week of treatment, treatment groups were given single dose of high glucose intake. Over 1, 2, and 3 hours of treatment with high glucose, the blood samples were collected for post-test examination. The data were then analysed by one way anova and paired-t test, and the result showed a significant increase of blood glucose and MDA in group 1 (p 〈 0,01), significant decrease of total antioxidant in group 1 (p 〈 0.01). In group 3, all of the parameters were different with group 1 and group 2 (p 〈 0.01). In group 4, MDA decreased significantly after treatment and the total antioxidant was increased significantly (p 〈 0.01). From these findings, it can be concluded that ethanol extract of purple sweet potato tubers can maintain the blood glucose level within normal limit, prevent the increase of MDA, and increase total antioxidant of the blood after high glucose intake in rats. The effective dose of the extract in this research was medium dose.  相似文献   

5.
Background: Studies indicate that people with a mental disability are less engaged in physical activity than their peers. The published data was mainly collected from oral feedback and the measurements taken from the use of pedometers. People with a mental disability engage in different types of physical activity, not only walking. The intention of this study was to assess physical activity using an accelerometer during a Special Olympics competition. Objective: To measure the physical activity of athletes with a mental disability during the Special Olympics national program using an accelerometer and to analyze the level of physical activity in relation to different disciplines, and in accordance with the gender of the participants. Methods: 75 athletes with a mental disability (50 males and 25 females) wore a GT3X ActiGraph to record their physical activity levels for two days during the Athletics Games in Olomouc, Czech Republic. Results: (1) The physical activity levels of the athletes met the published guidelines; (2) athletes who participated in both track and field events do not have higher energy expenditure than those participating only in field events; (3) athletes with a greater sporting ability are more physically active; (4) male athletes do not have a higher physical activity level. Conclusion: Regarding the level of physical activity, the local Special Olympic program is beneficial for people with a mental disability.  相似文献   

6.
利用TALENs技术制备瘦素基因敲除的大鼠   总被引:1,自引:1,他引:0       下载免费PDF全文
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7.
胰岛素抵抗大鼠 Orexin/leptin系统变化及其影响因素的研究   总被引:2,自引:2,他引:0  
目的研究IR大鼠下丘脑及脂肪组织中orexin和leptin系统的变化,分析其可能的调控因素.方法IR大鼠模型采用高脂肪膳食诱导并经钳夹技术证实;RT-PCR技术检测orexin/leptin及其受体(OX1R、OX2R、LR)mRNA的表达;生化比色法测定血清FFA、放免法测定血清TNF-α.结果该模型大鼠下丘脑中Prepro-orexin表达减少约80%,OX1R、OX2R分别增加3.4及3.2倍,leptin mRNA增加约8倍;LR减少78%;血清FFA和TNF-α均升高;钳夹技术中葡萄糖输注率(GIR60-120)明显低于对照组.结论高脂肪膳食可诱导大鼠体内IR;并导致orexin/leptin系统平衡状态的破坏;orexin与leptin相互作用共同维持机体能量代谢的稳定:FFA和TNF-α可能参与该系统的调控.  相似文献   

8.
目的 建立两种慢性肾衰竭大鼠模型,观察瘦素蛋白在大鼠组织、器官中的表达.方法 建立两种慢性肾衰竭CRF动物模型:(1)大鼠肾大部分切除诱发肾衰(Platt法).(2)腺嘌呤诱发大鼠慢性肾衰竭的动物模型(Yokozawa法).分别测定血清中血尿素氮(BUN),血肌酐(Scr)Ca2+、P5+等含量.取肾脏组织,HE染色,行免疫荧光,检测瘦素蛋白在两种慢性肾衰竭大鼠模型中的表达情况.结果 模型组大鼠血清中血尿素氮(BUN),血肌酐(Scr)等含量明显升高,免疫荧光检测显示两种模型大鼠肾脏组织瘦素蛋白的表达.结论 成功建立两种慢性肾衰竭CRF动物模型,显示不同模型组织部位的瘦素蛋白的表达.为进一步探讨瘦素蛋白在动物体内的生物学作用提供实验基础.  相似文献   

9.
郭春丽 《医学综述》2011,17(1):44-47
肥胖是多种因素相互作用导致能量代谢紊乱的结果。瘦素及瘦素受体的发现是肥胖调节分子机制研究领域的新热点。瘦素通过作用于中枢神经系统的受体和调节脑内食欲相关中枢神经元的活动而抑制摄食和增加能量消耗。此外,瘦素水平升高与肥胖共存又提示肥胖者体内存在瘦素抵抗现象。探讨其作用的神经机制和瘦素抵抗方面的进展是研究肥胖发生的新方向。  相似文献   

10.
We investigated the relationship between circulating leptin and osteoprotegerin (OPG) levels and insulin resistance assessed by HOMA-IR in premenopausal obese and normal weight women. Thirty four obese women (age 31 +/- 8 years) (BMI 35 +/- 4 kg/m(2)) with 19 healthy controls (age 31 +/- 7 years) (BMI <25 kg/m(2)) (BMI 21 +/- 2 kg/m(2)) were included in the study. Women were healthy and had no osteoporosis. Circulating leptin levels were significantly higher in obese women (17.11 +/- 2.05 ng/mL vs. 8.38 +/- 4.71 ng/mL, p <0.0001) and decreased OPG levels were found (14.7 +/- 7.15 pg/mL vs. 19.17 +/- 6.37 pg/mL, p = 0.03). Leptin showed a positive correlation with BMI (r = 0.851, p <0.0001), waist-to-hip ratio (r = 0.692, p <0.0001), fasting insulin (r = 0.441, p <0.001), HOMA-IR (r = 0.412, p = 0.002), fibrinogen (r = 0.387, p = 0.004), uric acid (r = 0.293, p = 0.033), hematocrit (r = 0.394, p = 0.003), systolic (r = 0.504, p <0.0001), and diastolic blood pressure (r = 0.363, p = 0.008). OPG showed a negative correlation with insulin (r = -0.341, p = 0.013) and HOMA-IR (r = -0.324, p = 0.018). In obese women group, the regression equation of HOMA-IR was (HOMA-IR = [0.095 x leptin]-[0.051 x OPG] + 1.71). However, there was no relation between leptin and OPG levels. In conclusion, circulating leptin and OPG levels were related to insulin resistance in premenopausal obese women. However, leptin had no interference in OPG in premenopausal women.  相似文献   

11.
血清瘦素浓度与血压的相关性研究   总被引:32,自引:2,他引:30  
目的 探讨血清瘦素与高血压,体重指数(BMI),能量代谢间的关系。方法 测定64例男性原发性高血压患者及54例男性正常血压者的血清瘦素浓度,收缩压(SBP)、舒张压(DBP)、BMI、血糖(Glu)甘油三酯(TG)总胆固醇(TC)高密度脂蛋白(HDL),低密度脂蛋白(LDL)等指标。血清瘦素用放射免疫法测定。分析瘦素与其它各项参数的相关性。结果 (1)两组(118例)的血清瘦素浓血压组血清瘦素浓度  相似文献   

12.
目的 探讨Leptin对体外培养的缺氧状态下视网膜祖细胞(RPCs)增殖、分化的影响及细胞中PTEN蛋白表达的变化。方法 原代培养大鼠RPCs,不同浓度Leptin作用RPCs细胞,分为:常氧培养组(Control组)、缺氧培养(Hypoxia)+0、0.3、1.0、3.0、10、30 nmol/L Leptin组,分别培养至12、24、48 h,CCK-8法检测细胞增殖活性。将原代培养的RPCs细胞分为:Control组、Hypoxia组、Hypoxia+Leptin组,培养48 h后,转换为分化培养基继续培养6 d,采用免疫荧光染色法对GFAP阳性细胞比例和β-tubulin III阳性细胞比例进行统计分析。Control组、Hypoxia组、Hypoxia+Leptin组细胞培养48 h后,采用Western blot法检测各组RPCs中PTEN蛋白表达水平。结果 原代培养的P0代RPCs为圆形悬浮生长,培养2 d后细胞可聚集成神经球。低浓度Leptin(0.3、1.0、3.0 nmol/L)作用RPCs 48 h,细胞增殖活性较Control组及Hypoxia组增强,RPCs细胞增殖活性随Leptin浓度增高呈递增趋势,其中,3.0 nmol/L Leptin作用48 h细胞增殖活性最强(P<0.05);高浓度Leptin(10 nmol/L,30 nmol/L)组细胞增殖活性较对照组减弱(P<0.05)。细胞培养48 h,与Control组及Hypoxia组相比,Hypoxia+Leptin组β-tubulin III阳性细胞比例和GFAP阳性细胞比例均无显著性差异(P>0.05),而PTEN蛋白表达量较对照组显著下调(P<0.05)。结论 低浓度Leptin可促进缺氧状态下大鼠RPCs细胞增殖,抑制细胞中PTEN蛋白表达,对细胞分化无明显影响。  相似文献   

13.
目的:通过大鼠糖尿病性心肌病(DCM)模型,探讨瘦素对白细胞介素-6(IL-6)、血管紧张素-Ⅱ(Ang-Ⅱ)的影响.方法:采用腹腔注射链脲佐菌素(STZ)造大鼠模型.将DCM大鼠随机分为DCM组、瘦素50μg/kg组、瘦素100μg/kg组,每组10只,3组大鼠造模成功后均继续给予高脂高糖饮食,瘦素50 μg/kg组、瘦素100μg/kg组分别给予每日腹腔注射瘦素50μg/kg、100μg/kg,持续5d.另设正常对照组10只给予常规饲料,4组的饲养时间均为12周.12周后检测血清IL-6、Ang-Ⅱ水平,并行心脏彩超测定大鼠的左室舒张末压(LVEDP)、左室舒张末期内径(LVIDd)及左室射血分数(LVEF).结果:与对照组相比,DCM组大鼠出现心功能减退,IL-6、Ang-Ⅱ水平升高(P<0.01);不同剂量的瘦素干预后,大鼠心功能减退严重,IL-6、Ang-Ⅱ水平也显著升高(P<0.01),且瘦素100μg/kg组变化更为明显.结论:瘦素可能在糖尿病心肌病的发生发展中起着重要作用,其机制可能是通过激活部分炎症因子及肾交感神经系统实现的.  相似文献   

14.
15.
Hyper-pigmentation is a common, acquired dermatological skin-disorder manifesting and identifiable as irregular brown or greyish-brown facial discolouration, and sometimes referred to as melanosis, melasma or hypermelanosis. Purpose and Objective: To identify the site of melanin deposition in skin-layers regarding facial hyper-pigmentation, based on a histological study of full-thickness skin-facial biopsies in aged Caucasian-cadavers. Hypothesis: Recalcitrant hyper-pigmentation, is chiefly characterised by hyper-melanosis restricted to the dermal-layer of the integument. Method: The histological features of facial hyper-pigmentation and solar-lentigenes were evaluated in a pilot-study of 5-randomly selected Caucasian-cadavers with pigmentation (15 facial biopsies), ranging in age between 75 and 102 years (mean 77-years). Selection-criteria included, both genders, age 〉 75, focal and confluent hyper-pigmented lesions, involving sun-exposed areas of skin (centrifacial, scalp, malar, mandibular and cervical). Study groups included (Grp-1: Control skin-histology in otherwise normal aged, human-cadavers; Grp-2: Histology of pigmented facial skin-lesions in man; Grp-3: Comparative histological skin-controls in non-human primates). No obvious hepatic disease was evident in the cohort studied. Twenty-five histological controls were obtained from non-pigmented areas. Histological evaluation of full-thickness skin-biopsies (including the lesion, edge and peri-]esion skin), was under a Leitz~-light-microscope, and staining included H&E, Masson-trichrome, Masson-fontana, Alcian-blue and Verhoef technology. Histological-scoring used was on histological deposition of melanin in skin-layers: epidermal, dermal, mixed, and indeterminate melanin-deposition (score 1-4). Controls included cadaveric skin-biopsies of human races of colour and non-human primate, Cercopethicus Aethiops (latter is known to have predominantly dermal-melanin deposition). Pigmented and non-pigmented areas were compared in both species. Results: The majority of clinically visible individual and confluent areas of hyper-pigmentation studied were maeroscopically present on the forehead, frontal scalp in hair-receded cadavers, molar and temporal zones. Histologically, documented features of age-related changes without pigment were present in almost all the embalmed cadaver-skins, with a melanin-score of 1. Computer enhanced skin geometry and biometrics confirmed the presence of an aged-skin, pigmentation and features of solar damage. The human embalmed-tissue was well preserved and minimal autolytic changes were present. Special stains of full-thickness biopsies (Masson-Fontana), showed that melanin in the subhuman-primate is lodged in the deep dermis (reticular dermis), within the extra-cellular matrix (ECM) and superficial to the hypodermal adipose-tissue (melanin-score 3). Fifteen pigmented lesions studied in five (5) aged-cadavers (forehead, molar and mandibular areas) all showed predominantly epidermal-deposition of melanin in the basal, suprabasal and stratum corneum with tiny focal areas of dermal melanosis in single-cell macrophages in the papillary-dermis but not reticular-dermis (melanin-score 2). A melanin-deposition localization ratio of epidermis to dermis was approximately 98 to 2% in cadavers with hyper-pigmentation. Conclusion: The skin-strata localization of the melanin with regards hyper-pigmentation of the face and forehead in this aged, human adult Caucasian, cadaveric-study, was predominantly in the epidermis and sparse in the papillary dermis.  相似文献   

16.
目的:探讨恶性肿瘤患者营养状况与血清瘦素、CD4^ T/CD8^ T细胞比值的关系。方法:选择恶性肿瘤患者79例及BMI为18.5~25.0的42例健康者,检测血清瘦素浓度和CD4^ T/CD8^ T细胞比值。结果:(1)不同营养状态的恶性肿瘤患者的血清瘦素含量之间均有显著性差异,而CD4^ T/CD8^ T细胞比值之间均无显著性差异。(2)女性肿瘤患者的血清瘦素含量明显高于男性患者。(3)BMI为18.5~25.0的恶性肿瘤患者与健康人血清瘦素含量之间无显著性差异,而肿瘤组CD4^ T/CD8^ T细胞比值明显低于健康人。(4)以瘦素为因变量,BMI、性别、年龄、CD4^ T/CD8^ T细胞比值为自变量进行多元线性回归分析,结果显示,血清瘦素含量与BMI、性别显著相关。结论:恶性肿瘤合并营养不良者,血清瘦素水平明显低于营养正常和肥胖的肿瘤患者。血清瘦素含量女性高于男性。BMI正常的肿瘤患者血清瘦素含量与正常人无差异,说明此时瘦素还发挥正常调节作用。在影响恶性肿瘤患者血清瘦素含量的因素中,BMI、性别是最主要的因素。不同营养状况的肿瘤患者之间的血清瘦素水平有明显差异,而与其相对应CD4^ T/CD8^ T细胞比值无统计学差异,提示瘦素影响免疫反应可能有更复杂的途径和机制,值得进一步探讨。  相似文献   

17.
Objective:To describe the use of the GlideScope in comparison with direct laryngoscopy for elective surgical patients requiring tracheal intubation. Methods:Two hundred patients, ASA Ⅰ - Ⅱ scheduled for elective surgery under general anesthesia requiring orotracheal intubation were selected. Information was collected identifying the patient demographics and airway assessment features (Mallampati oropharyngeal scale, thyromenta distance and mouth opening). In a random crossover design, after induction of anesthesia and neuromuscular block, the laryngoscopes were inserted in turn, and the views of the glottis at laryngoscopy (Cormack and Lehane scores) were compared. The tracchea was intubated using either the standard Macintosh laryngoscope or GlideScope after the second grading at laryngoscopy was done. Complications associated with intubating were recorded. Results: There were 200 patients including 107 males and 93 females, with mean age being 52±13 years, height 164.8±11.3 cm, weight 64.0±11. 5 kg, thyromental distance 6. 9± 1.1 cm, and mouth opening 5.7±0.5 cm. There was a significant association between the preoperative view of the oropharynx (Mallampati score) and the view of the glottis at laryngoscopy for both the direct Macintosh laryngoscope (P〈0. 001) and the GlideScope (P〈0. 001). Among 200 patients, 106 patients had the same C&L grade, 91 of remaining patients showed improvement in the C&L grade (P〈0. 001 ) obtained with GlideScope compared with the direct Macintosh laryngoscope. 3 of remaining patients showed better view of the glottis(C&L grade) with the direct Macintosh laryngoscope (grade 1) than with GlideScope (grade 2). There were no cases of failure to be intubated. There were no cases of dental or mucosal injury in all patients. Conclusion: GlideScope videolaryngoscope yielded comparable or superior laryngeal view compared with Macintosh laryngoscope. The new type of laryngoscope may have potential advantages for managing the d  相似文献   

18.
The aim of this study was to purify and characterize a keratinase produced by a new isolated Bacillus subtilis KD-N2 strain. The keratinase produced by the isolate was purified using ammonium sulphate precipitation, Sephadex G-75 and DEAE (diethylaminoethyl)-Sepharose chromatographic techniques. The purified enzyme was shown to have a molecular mass of 30.5 kDa, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The optimum pH at 50 ℃ was 8.5 and the optimum temperature at pH 8.5 was 55 ℃. The keratinase was partially inactivated by some metal ions, organic solvents and serine protease inhibitor phenylmethanesulfonyl fluoride (PMSF). Sodium dodecyl sulfate (SDS) and ethylene diamine tetraacetic acid (EDTA) had positive effect on the keratinase activity. Reducing agents including dithiothreitol (DTT), mercaptoethanol, L-cysteine, sodium sulphite, as well as chemicals of SDS, ammonium sulfamate and dimethylsulfoxide (DMSO) stimulated the enzyme activity upon a feather meal substrate. Besides feather keratin, the enzyme is active upon the soluble proteins ovalbumin, bovine serum albumin (BSA), casein and insoluble ones as sheep wool and human hair. Calf hair, silk and collagen could not be hydrolyzed by the keratinase.  相似文献   

19.
Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regu- lated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autop- hagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.  相似文献   

20.
Abnormal intracellular accumulation or transport of lipids contributes greatly to the pathogenesis of human diseases. In the liver, excess accumulation of triacylglycerol (TG) leads to fatty liver disease encompassing steatosis, steatohepatitis and fibrosis. This places individuals at risk of developing cirrhosis, hepatocellular carcinoma or hepatic decompensation and also contributes to the emergence of insulin resistance and dyslipidemias affecting many other organs. Excessive accumulation of TG in adipose tissue contributes to insulin resistance as well as to the release of cytokines attracting leucocytes leading to a pro-inflammatory state. Pathological accumulation of cholesteryl ester (CE) in macrophages in the arterial wall is the progenitor of atherosclerotic plaques and heart disease. Overconsumption of dietary fat, cholesterol and carbohydrates explains why these diseases are on the increase yet offers few clues for how to prevent or treat individuals. Dietary regimes have proven futile and barfing surgery, no realistic alternatives are at hand as effective drugs are few and not without side effects. Overweight and obesity-related diseases are no longer restricted to the developed world and as such, constitute a global problem. Development of new drugs and treatment strategies are a priority yet requires as a first step, elucidation of the molecular pathophysiology underlying each associated disease state. The lipid droplet (LD), an up to now over- looked intracellular organelle, appears at the heart of each pathophysiology linking key regulatory and metabolic processes as well as constituting the site of storage of both TGs and CEs. As the molecular machinery and mechanisms of LDs of each cell type are being elucidated, regulatory proteins used to control various cellular processes are emerging. Of these and the subject of this review, small GTPases belonging to the Rab protein family appear as important molecular switches used in the regulation of the intracellular trafficking and storage of lipids.  相似文献   

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